Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies

Abstract

IntroductionThe Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing of non-rodents during telemetry recordings in safety pharmacology and toxicology studies. The aim was to share experiences, canvas opinion on the study procedures/designs that could be used and explore the barriers to social housing.MethodsThirty-nine sites, either running studies (Sponsors or Contract Research Organisations, CROs) and/or outsourcing work responded to the survey (51% from Europe; 41% from USA).ResultsDuring safety pharmacology studies, 84, 67 and 100% of respondents socially house dogs, minipigs and non-human primates (NHPs) respectively on non-recording days. However, on recording days 20, 20 and 33% of respondents socially house the animals, respectively. The main barriers for social housing were limitations in the recording equipment used, study design and animal temperament/activity. During toxicology studies, 94, 100 and 100% of respondents socially house dogs, minipigs and NHPs respectively on non-recording days. However, on recording days 31, 25 and 50% of respondents socially house the animals, respectively. The main barriers for social housing were risk of damage to and limitations in the recording equipment used, food consumption recording and temperament/activity of the animals.ConclusionsAlthough the majority of the industry does not yet socially house animals during telemetry recordings in safety pharmacology and toxicology studies, there is support to implement this refinement. Continued discussions, sharing of best practice and data from companies already socially housing, combined with technology improvements and investments in infrastructure are required to maintain the forward momentum of this refinement across the industry.

Improving quality of science through better animal welfare: the NC3Rs strategy

“…The outputs are published in the peerreviewed literature and are promoted at major scientific conferences and in research organizations. Working groups have focused in areas in which refinement can have a substantial effect, including rodent models of epilepsy 24 and stroke, food and fluid restriction in macaque behavioral neuroscience 25 , and toxicology studies (for example, microsampling, social housing during cardiovascular recordings 26 and body weight loss limits for acute studies 27 ). The expert working group on mammalian models of epilepsy, convened to review current practice and identify opportunities to improve animal welfare, was instigated at the request of academics from the epilepsy research community (http://www.nc3rs.org.…”

Supportive care for animals on toxicology studies: An industrial best practices survey conducted by the IQ 3Rs TPS CRO Outreach Working Group

“…Similar surveys between sponsors and CROs have been conducted for benchmarking social housing of non-rodents for safety pharmacology. 32,33 Several respondents shared unique supportive care strategies that were employed with no impact on regulatory submissions. These cases included gavage feeding as supportive care for appetite loss in dogs (animals had >25% body weight loss with no additional clinical signs), animals pre-dosed with high caloric liquid nutritional supplement (in cases where animals had to be dosed in a fed state) that contributed to good clinical condition of the animals, and treatment with fluids, antidiarrheals, probiotics, and fiber in sub-chronic studies involving gastrointestinal signs.…”

Opportunities to Apply the 3Rs in Safety Assessment Programs

“…Though the published recommended study designs based on cross-company data sharing include suggestions for group sizes ( Chapman et al 2009 ; Prior et al 2016 ; Sparrow et al 2011 ), the general regulations relating to pharmaceutical development themselves do not specify preferred group size. The only ICH guideline to suggest a specific dosing group size is ICH S9 for oncology indications, which suggests group sizes of “at least 3 animals/sex/group, with an additional 2/sex/group for recovery” for nonrodents.…”

“…This is usually performed as a safety pharmacology telemetry study ( Leishman et al 2012 ) and/or integrated into toxicology studies ( Guth et al 2009 ), particularly for biopharmaceuticals or anticancer agents when a stand-alone safety pharmacology study is not always required ( ICH S6(R1) , S9 ; Vargas et al 2008 ). Although it is general practice to socially house nonrodents on nontelemetry recording days, the majority of the industry will separate animals for data collection on the specific telemetry recording days within a study, partly due to limitations in the equipment used and perceptions on animal activity/data variability ( Prior et al 2016 ). However, these barriers can be overcome as many companies upgrade to new equipment (that allows for social housing) in the future and data from companies successfully socially housing are shared ( Kaiser et al 2015 ; Klumpp et al 2006 ; Xing et al 2015 ).…”